Cationic liposome-mediated efficient induction of type I interferons by a low dose of poly I:poly C in mouse cell
S Okamoto1, Y Watanabe, Y Takakura
1Departments of Drug Delivery Research Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Insights
Complexing poly I:poly C with cationic reagents like Lipofectin significantly enhances type I interferon (IFN) induction. This method uses lower, non-cytotoxic doses and short treatment times, showing potential for clinical applications.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Double-stranded polyriboinosinic acid:polyribocytidylic acid (poly I:poly C) effectively induces type I interferons (IFNs).
- High doses of poly I:poly C required for efficient IFN induction can be cytotoxic.
Purpose of the Study:
- To investigate the IFN-inducibility of poly I:poly C complexed with cationic reagents.
- To determine if complexation can reduce the required dose and cytotoxicity of poly I:poly C for IFN induction.
Main Methods:
- Poly I:poly C was complexed with cationic reagents (Lipofectin, LipofectACE).
- Interferon (IFN) production was measured in mouse fibroblast L cells treated with these complexes.
- Cytotoxicity and optimal treatment conditions (dose, time) were assessed.
Main Results:
- Lipofectin and LipofectACE complexes induced substantial type I IFNs (mostly beta-type) at doses two orders lower than poly I:poly C alone.
- Optimal induction occurred at 0.1 microgram/ml poly I:poly C with 2-10 microgram/ml of Lipofectin/LipofectACE.
- These conditions showed no significant cytotoxicity and required short treatment times (<10 min).
Conclusions:
- Complexing poly I:poly C with Lipofectin or LipofectACE enhances IFN induction efficacy.
- This novel method allows for lower, non-cytotoxic doses and short treatment durations.
- The approach is applicable across cell types and species, suggesting potential for clinical use in IFN induction.
Abstract:
Double-stranded polyriboinosinic acid:polyribocytidylic acid (poly I:poly C) is a powerful inducer of type I interferons (IFNs). However, the dose of poly I:poly C required for efficient IFN induction is so high as occasionally to be cytotoxic. In this work, we examined the IFN-inducibility of poly I:poly C complexed with several cationic reagents in mouse fibroblast L cells and found that Lipofectin and LipofectACE can induce the production of a substantial amount of type I IFNs (mostly beta-type) even at a two-order lower dose compared with poly I:poly C alone. Such effects of poly I:poly C were optimal at 0.1 microgram/ml for 2-10 microgram/ml of Lipofectin and LipofectACE. These conditions caused no significant cytotoxicity in the recipient cells. Furthermore, a short treatment (less than 10 min) with the complexes was sufficient for the maximum induction. This IFN induction method was applicable to other cell types and other species including human. Hence, our observations may pave the way for clinical application of the IFN inducer.
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